1. Field of the Invention
This invention relates to the production by a novel chemical synthesis of particular members of the cephalosporin family of antibiotics characterized by having 2-aminomethylphenylacetamido as their 7-substituent.
2. Description of the Prior Art
7-(2-Aminomethylphenylacetamido)-3-(1-carboxymethyltetrazol-5-ylthiomethyl) -3-cephem-4-carboxylic acid is a potent injectable cephalosporin having the generic name ceforanide; it has also been called BL-S786 in the literature. It was described, for example, in U.S. Pat. No. 4,100,346.
U.S. Pat. No. 4,118,563 describes the preparation of ceforanide by the reduction with hydrogen and Raney nickel of the corresponding 2-azidomethyl compound.
Older preparations and uses of hydrides of boron were described, for example, by Burg and Schlesinger, J. Amer. Chem. Soc. 59, 780-787 (1937). Complexes of BH.sub.3 (also called borine) with amines were disclosed by Brown in U.S. Pat. Nos. 2,860,167 and 3,035,904. The borane-amine complexes were reviewed by Lane in Aldrichimica Acta, 6(3), 51-58 (1973) and many of them are commercially available. For the use of boranes (but not the amine complexes) to reduce organic azides to secondary amines see Suzuki, J. Amer. Chem. Soc. 93, 4329-30 (1971).
The object of the present invention was to provide a process similar to that of U.S. Pat. No. 4,118,563 which did not require the use on a commercial scale of expensive special equipment used for that type of hydrogenation.